crossing96/oncoscreening huggingface dataset:
High NF-κB and STAT3 activity in human urothelial carcinoma: a pilot study.	PURPOSE: Given that the tumor-promoting inflammation has been previously established in squamous cell carcinoma of the bladder but its contribution to development of urothelial carcinoma (UC) still remains elusive, our aim was to study changes in expression and activity of inflammation-mediating NF-κB and STAT3 transcription factors in human urothelial bladder carcinoma as well as expression of their target genes cyclin D1, VEGFA and TGFβ1. METHODS: Gene expression of STAT3, NF-κB, TGFβ1, cyclin D1 and VEGFA was measured by quantitative real-time polymerase chain reaction in both tumor and healthy bladder tissue from 36 patients with UC of the bladder. Activation of STAT3 and NF-κB was assessed with immunohistochemistry and immunoblot. RESULTS: Urothelial bladder carcinoma displayed elevated expression as well as activation of NF-κB (P = 5.38e-10) and STAT3 (P = 0.002) transcription factors. Furthermore, elevated level of expression was observed for cyclin D1, VEGFA and TGFβ1 (P = 9.71e-09, P = 9.71e-09, P = 5.38e-10). Preliminary statistical analysis indicated that the level of upregulation of STAT3 or NF-κB was probably not dependent upon the grade (P = 0.984 and 0.803, respectively) and invasiveness of the tumor (0.399 and 0.949), nor to the gender (0.780 and 0.536) and age (0.660 and 0.816) of the patients. CONCLUSIONS: NF-κB and STAT3 signaling pathways, as main inflammatory mediators, are found to be activated in urothelial bladder carcinoma indicating that chronic inflammatory processes are accompanying development of this tumor type. Future studies will have to determine possible causative role of inflammatory processes in development of urothelial bladder carcinomas.	bladder
Long-term changes in renal function outcomes following radical cystectomy and urinary diversion.	BACKGROUND: We analyzed long-term changes in the renal function of patients undergoing radical cystectomy and urinary diversion (UD). METHODS: This study included 169 patients who underwent radical cystectomy and UD (42, cutaneous ureterostomy; 40, ileal conduit; 87, neobladder substitution), and were followed for at least 60 months (median 106 months). Renal deterioration was defined as a >25 % decrease in the estimated glomerular filtration rate (eGFR) relative to that prior to surgery. We determined the associations between several parameters and postoperative renal deterioration. RESULTS: Despite the significantly younger age and more favorable renal function of patients with neobladder substitution than of those with other types of UD, no significant differences were observed in the remaining preoperative clinical parameters among the three different UD groups. The mean eGFR of the 169 patients decreased from 69.6 to 55.9 mL/min/1.73 m(2), and renal deterioration was observed in 24 (57.1 %), 20 (50.0 %) and 34 (39.0 %) patients in the cutaneous ureterostomy, ileal conduit and neobladder substitution groups, respectively. Multivariate analysis of several parameters identified the presence of baseline hypertension and an episode of acute pyelonephritis, but not the type of UD, as significant predictors of postoperative renal deterioration. CONCLUSIONS: The incidence of renal deterioration was comparatively high following radical cystectomy, irrespective of the type of UD. Special attention should be paid to the long-term preservation of renal function in these patients, particularly those with hypertension and/or episodes of acute pyelonephritis.	bladder
Inhibition of grade dependent autophagy in urothelial carcinoma increases cell death under nutritional limiting condition and potentiates the cytotoxicity of chemotherapeutic agent.	PURPOSE: We evaluated the status of autophagy in different grades of urothelial carcinoma and explored autophagy modulators as a potential adjunctive therapeutic agent for urothelial carcinoma. MATERIALS AND METHODS: The study was performed in tumor tissue from patients with low and high grade urothelial carcinoma, in normal urothelial tissue and in the T24 cell line. Autophagic vesicles and the expression of various autophagic proteins were studied in tissue samples by transmission electron microscopy and Western blot, respectively. The effect of autophagy induction and inhibition was evaluated by measuring AMPK and mTOR expression, cell viability and mitochondrial membrane potential. The therapeutic implication of autophagy was studied using cisplatin alone or combined with an autophagy inhibitor. RESULTS: High grade urothelial carcinoma showed a higher number of autophagic vesicles and significantly higher expression of autophagic proteins. Upon starvation cells cultured from high and low grade urothelial carcinoma demonstrated significant autophagy induction associated with AMPK activation and mTOR inhibition. AMPK inhibition decreased the autophagic response and increased cell death. Autophagy inhibition by wortmannin, 3-methyladenine and chloroquine increased mitochondrial hypopolarization as well as caspase-9 and 3 dependent cell death. Combined treatment with cisplatin and an autophagy inhibitor resulted in greater cell death than cisplatin treatment alone. CONCLUSIONS: Autophagy is related to urothelial carcinoma grade and regulated via the AMPK pathway for tumor cell survival. Autophagy inhibition leads to cancer cell death through an intrinsic apoptotic pathway. The potential application of autophagy inhibitors as an adjunct to chemotherapy for urothelial carcinoma must be explored.	bladder
The role of microRNA profiling in prognosticating progression in Ta and T1 urinary bladder cancer.	OBJECTIVE: To analyze microRNA profile in Ta and T1 urinary bladder cancers in combination and separately and to relate this to the risk of later developing higher-stage disease. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded samples of 44 Ta and 42 T1 bladder cancers representing cases with and without stage progression during follow-up were collected and microRNA expression levels were measured by microarray analysis. RESULTS: In a comparison between the progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were differentially expressed. miR-10a-5p was also correlated to time to progression (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and miR-130a-3p, were differentially expressed among Ta tumors and had a fold change of more than 1.5 (P<0.038). The comparison concerning microRNA expression between the progressors and controls in category T1 cancers revealed no significant differences. CONCLUSIONS: Profiling revealed that certain microRNAs predicted the risk of developing higher-stage disease among patients with Ta cancers. Lower miR-10a-5p expression in Ta progressing tumors indicates that this microRNA could be important for later malignant potential among this group of patients.	bladder
Impact of chemokines CCR5∆32, CXCL12G801A, and CXCR2C1208T on bladder cancer susceptibility in north Indian population.	Chemokines are small inducible pro-inflammatory cytokines. In the present study, we tested association of chemokine single nucleotide polymorphisms (SNPs) viz., CCR5∆32, CXCL12G801A and CXCR2C1208T genes in bladder cancer (BC) patients and normal healthy controls of north Indians. Genotyping of the above SNPs were done in 200 BC cases and 200 healthy controls, using RFLP and amplification refractory mutation system-polymerase chain reaction methodology. A significant association was found in CXCL12G801A with BC risk. In case of CXCL12G801A polymorphism, the heterozygous (GA) genotype showed significantly high risk (p < 0.001, odds ratio (OR) = 2.72), whereas A allele carrier (GA + AA) also showed risk with BC (p < 0.001, OR = 2.44). In CXCR2C1208T polymorphism, the variant genotype (TT) showed significant risk for BC (p = 0.028, OR = 1.58). The variant allele (T) of CXCR2C1208T polymorphism was found to be associated with BC risk (p = 0.003, OR = 1.29). Interestingly, smoking was also found to modulate 1.16-fold risks for BC in case of CXCR2C1208T, variant genotype (TT). Upon analyzing the gene-gene interaction between CXCR2C1208T and CXCL12G801A, the combination CT-GA showed 4-fold risk for BC (p = 0.009). Our results indicated that polymorphism in CXCR2C1208T and CXCL12G801A showed high risk for BC in north Indian population. However, CCR5∆32 exhibited no association. Study with large sample size and diverse ethnicity are required to validate these observations.	bladder
The prognostic value of P-cadherin in non-muscle-invasive bladder cancer.	OBJECTIVES: This research aims to specify the prognostic value of P-cadherin on recurrence and progression in non-muscle-invasive bladder cancers (NMIBC). METHODS: A total of 110 NMIBC cases were collected and P-cadherin protein was assessed by immunohistochemical test in these samples. Correlations between P-cadherin expression and clinicopathologic features were analyzed. For recurrence-free and progression-free survival, Kaplan-Meier log-rank test was used. Then Cox univariate and multivariate analyses were further performed. RESULTS: P-cadherin high expression correlated with tumor progression (P = 0.031). Kaplan-Meier results showed that patients with high P-cadherin expression had worse progression-free survival (P = 0.034) but not recurrence-free survival (P = 0.133) than low-expression patients. Cox regression results showed P-cadherin expression was an independent predictor for progression (P = 0.042) but not recurrence (P = 0.139) in NMIBC. CONCLUSIONS: Our results demonstrated that P-cadherin expression correlated with tumor progression and could be taken as an independent predictor for progression in NMIBC.	bladder
Argonaute 2 is up-regulated in tissues of urothelial carcinoma of bladder.	Argonaute 2 proteins (Ago2) have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and play key roles in carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore Ago2 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of Ago2 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of Ago2 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinic pathological analysis was showed a significant correlation existed between the higher expression of Ago2 protein with the Histological grade, lymph node metastasis and Distant metastasis (P<0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated Ago2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (62.2% VS 86.3%, P<0.05). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of Ago2 was an independent prognostic factor in UCB. CONCLUSIONS: These results suggest that the aberrant expression of Ago2 in human UCB is possibly involved with tumorigenesis and development, and the Ago2 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of Ago2 need to address these issues.	bladder
Cisplatin-induced epigenetic activation of miR-34a sensitizes bladder cancer cells to chemotherapy.	BACKGROUND: Accumulating evidence suggests a tumor suppressive role for miR-34a in human carcinogenesis. However, its precise biological role remains largely elusive. This study aimed to reveal the association of the miR-34a expression and its modulation of sensitivity to cisplatin in muscle-invasive bladder cancer (MIBC). METHODS: miR-34a expression in MIBC cell lines and patient tissues was investigated using qPCR. The methylation analysis of miR-34a promoter region was performed by MassARRAY. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vector were used to regulate miR-34a expression in MIBC cells to investigate its function in vitro and in vivo. RESULTS: miR-34a expression was frequently decreased in MIBC tissues and cell lines through promoter hypermethylation while it was epigenetically increased in MIBC cells following cisplatin treatment. Increased miR-34a expression significantly sensitized MIBC cells to cisplatin and inhibited the tumorigenicity and proliferation of cancer cells in vitro and in vivo. Furthermore, we identified CD44 as being targeted by miR-34a in MIBC cells following cisplatin treatment, and increased CD44 expression could efficiently reverse the effect of miR-34a on MIBC cell proliferation, colongenic potential and chemosensitivity. CONCLUSIONS: Cisplatin-based chemotherapy induced demethylation of miR-34a promoter and increased miR-34a expression, which in turn sensitized MIBC cells to cisplatin and decreased the tumorigenicity and proliferation of cancer cells that by reducing the production of CD44.	bladder
New treatments for bladder cancer: when will we make progress?	The prognosis and long-term survival for patients with metastatic urothelial carcinoma patients is poor. Traditionally, the mainstay of treatment has been combination chemotherapy with gemcitabine and cisplatin or with the classical M-VAC. Vinflunine has become an EMA-approved second-line option in Europe. Urothelial carcinomas contain genetic alteration in multiple genes that are potentially treated by targeted therapies. Recently, a number of these new therapies have been developed in this disease. But not one has been approved for clinical use in urothelial cancers. While clinical evaluation of these agents is still in its early days, some promising findings have begun to emerge. For example, everolimus demonstrated activity in those metastatic urothelial cancer patients who harbors TSC1 mutation. With the identification of the most relevant drug targets for tumors initiation and maintenance and the best way to assess drug candidates that may only account for a small fraction of patients, it is anticipated that the therapeutic arsenal for urothelial cancers will be expanded in the future.	bladder
The predictive value of GSTT1 polymorphisms in predicting the early response to induction BCG therapy in patients with non-muscle invasive bladder cancer.	INTRODUCTION: We evaluated the predictive value of glutathione S transferase mu (GSTM1) and theta (GSTT1) polymorphisms in early response to bacillus Calmette-Guérin (BCG) induction therapy in patients with primary non-muscle invasive bladder cancer. METHODS: GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction using blood genomic DNA from 135 patients with primary non-muscle invasive bladder cancer who were being treated with a single induction course of BCG. BCG nonresponsiveness (early BCG failure) was defined as a tumor recurrence or progression within 12 months after BCG induction therapy. The predictive value of GST polymorphisms was evaluated by Kaplan-Meier analysis and multivariate logistic regression models. RESULTS: Patients carrying a GSTT1-positive genotype demonstrated a higher likelihood of early BCG failure regardless of cigarette smoking. After stratification based on the tumor stage and grade, the high-risk group (T1G3) with a GSTT1-positive genotype showed a 14-fold higher risk of early BCG failure compared with those with a GSTT1-null genotype. In a combined analysis of 2 genes, the GSTT1-positive/GSTM1-null genotype had a higher risk of BCG nonresponsiveness compared with the GSTT1-null/GSTM1-null genotype (odds ratio = 4.17, 95% CI: 1.54-11.26). By multivariate logistic regression analysis, the GSTT1-positive genotype was an independent predictor of early BCG failure (odds ratio = 3.67, 95% CI: 1.61-8.38). Kaplan-Meier estimates revealed a significant difference in disease-free survival depending on the GSTT1 genotype (log rank test, P = 0.038). CONCLUSIONS: The results of this study suggest that the GSTT1-positive genotype is an independent predictor of early BCG failure. These results can help determine whether patients would benefit from adjuvant BCG treatment or may require more aggressive alternative therapies.	bladder
Effect of intravesical immunotherapy on sperm parameters in young patients with non--muscle-invasive bladder carcinoma: prospective analysis.	INTRODUCTION: To investigate the effects of intravesical immunotherapy on semen parameters in young patients with non-muscle invasive bladder tumour. METHODS: A total of 17 sexually active male patients < 45 years of age underwent transurethral resection of bladder tumour (TURBT) from Jan 2010 to Dec 2012. On HPE analysis, T1 high grade was found in 16 patients and Ta grade high grade in 1 patient. Associated CIS was found in 4 patients. Induction course of 6 weeks of adjuvant BCG therapy was given. Semen analysis was done 1 week prior to BCG therapy and 3 months after BCG therapy. Serum levels of hormones like total testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also measured. RESULTS: Mean age of patients at diagnosis was 34.6 (29-43) years. Total semen volume was found to be decreased in 2 patients. Main parameter which was deteriorated was total sperm concentration which was significantly decreased in 12 patients and 5 patients even had their counts below oligospermia levels. Seven patients had associated decrease in sperm motility. However, no patient showed significant difference in other semen parameters. Also no patient had any change in androgen hormonal status except 2 patients in which serum testosterone was found to be non-significantly decreased. CONCLUSION: Intravesical therapy with BCG was found to adversely affect spermatogenesis and cause oligospermia. It is important that relatively young patients must be informed of these effects and advised to have sperm preservation before instillation of BCG therapy to avoid fertility issues in future.	bladder
Risk of cancer, with special reference to extra-intestinal malignancies, in patients with inflammatory bowel disease.	AIM: To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local population. METHODS: This was a prospective, observational, 7-year follow-up, cohort study. Cumulative incidence, incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background population. The incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de Fuenlabrada. Demographic data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer, disease extent, inflammatory bowel disease treatment, cancer therapy and cancer evolution were also collected in the inflammatory bowel disease cohort. RESULTS: Eighteen of 590 patients with inflammatory bowel disease developed cancer [cumulative incidence = 3% (95%CI: 1.58-4.52) vs 2% (95%CI: 1.99-2.11) in the background population; RR = 1.5; 95%CI: 0.97-2.29]. The cancer incidence among inflammatory bowel disease patients was 0.53% (95%CI: 0.32-0.84) per patient-year of follow-up. Patients with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma (RR = 5.23, 95%CI: 1.95-13.87), appendiceal mucinous cystadenoma (RR = 36.6, 95%CI: 7.92-138.4), neuroendocrine carcinoma (RR = 13.1, 95%CI: 1.82-29.7) and rectal carcinoid (RR = 8.94, 95%CI: 1.18-59.7). Colorectal cancer cases were not found. CONCLUSION: The overall risk of cancer did not significantly increase in our inflammatory bowel disease patients. However, there was an increased risk of urinary bladder cancer and, with less statistical power, an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine tumors. Colorectal cancer risk was low in our series.	bladder
Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.	Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.	bladder
[Expression and significance of FGFR2IIIc in chemoresistant bladder cancer cells].	OBJECTIVE: To investigate the role of fibroblast growth factor receptor-2 (FGFR2) splice variant FGFR2IIIc in the regulation of mesenchymal-epithelial transition (MET) in doxorubicin-resistant bladder cancer cells. METHODS: A doxorubicin-resistant human bladder cell line (253J/DOX) was generated from the bladder cancer cell line 253J by being continuously exposed to gradually increasing doses of doxorubicin. Chemosensitivity to doxorubicin was determined by MTT assay. The expressions of P-glycoprotein and FGFR2IIIc were evaluated by Western blotting and real-time RT-PCR, respectively. Changes in E-cadherin and vimentin were detected by Western blot analysis. Migration ability of 253J and 253J/DOX cells was analyzed by in vitro wound healing assay. RESULTS: The resistant cells, 253J/DOX, were more resistant to doxorubicin than the parent cells. Western blotting and RT-PCR analysis indicated the higher levels of P-glycoprotein and FGFR2IIIc in 253J/DOX cells (P<0.05). Additionally, compared with the 253J cells, 253J/DOX cells presented the upregulation of E-cadherin, the downregulation of vimentin and the inhibition of migration ability. CONCLUSION: FGFR2IIIc-induced MET in chemoresistant bladder cancer cells may play an important role in the formation of metastatic lesions.	bladder
Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1.	MicroRNAs mainly inhibit coding genes and long non-coding RNA expression. Here, we report that hsa-miR-125b and oncogene SIRT7/oncogenic long non-coding RNA MALAT1 were inversely expressed in bladder cancer. Hsa-miR-125b mimic down-regulated, whereas hsa-miR-125b inhibitor up-regulated the expression of SIRT7 and MALAT1. Binding sites were confirmed between hsa-miR-125b and SIRT7/MALAT1. Up-regulation of hsa-miR-125b or down-regulation of SIRT7 inhibited proliferation, motility and increased apoptosis. The effects of up-regulation of hsa-miR-125b were similar to that of silencing MALAT1 in bladder cancer as we had previously described. These data suggest that hsa-miR-125b suppresses bladder cancer development via inhibiting SIRT7 and MALAT1.	bladder